It is proposed to characterize disease-induced alterations in the electrophysiologic properties of the isolated human heart which may cause the increased incidence of dysrhythmia in patients with heart disease. Preliminary glass microelectrode electrophysiologic studies on isolated specimens of normal and diseased human atrial appendage and papillary muscle obtained during corrective open-heart surgery have provided suggestive evidence that rheumatic and ischemic disease may alter many of the electrophysiologic and pharmacologic properties of the human heart. Among those electrophysiologic properties apparently altered (from normal) are: resting transmembrane potential, responsiveness, excitability, refractoriness and automaticity. These disease-induced changes will be characterized using standard glass microelectrode techniques on similarly obtained, isolated, perfused specimens of normal human heart (except for possible hypertrophy) and heart from patients with rheumatic or ischemic disease. Comparisons of the responses of normal and diseased specimens to certain physiologic and pharmacologic interventions will be made. Interventions will be selected to provide (1) information about possible mechanisms underlying disease-associated changes in electrophysiologic activity and (2) possible approaches for inhibition or reversal of the disease-induced alterations in cardiac electrical activity. This will include alteration of the ionic milieu, change in milieu temperature, exposure to pharmacologic agents reasonably expected to modify the electrophysiologic properties and application of current to the preparation. This research should (1) permit a systematic delineation of electrophysiologic changes associated with heart disease; (2) provide a basis for further study, using techniques such as the voltage clamp, or ionic and membrane mechanisms underlying changes in electrical activity associated with heart disease; (3) provide the basis for a more rational approach to the diagnosis and therapy of disease-induced dysrhythmia. BIBLIOGRAPHIC REFERENCES: Ten Eick, R. E., Singer, D. H. and Solberg, L. E.: Coronary occlusion: Effect on cellular electrical activity of the heart. Med. Clin. N. Am. 60:49-67, 1976.